Evaluation of relapse-free survival in T3N0 colon cancer: the role of chemotherapy, a multicentric retrospective analysis.

BACKGROUND: Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC. METHODS: RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively. RESULTS: 834 patients with T3N0 CC were recruited. Median age was 69 (29-93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1-76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3-24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints. In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005). CONCLUSIONS: Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC.

Pre-emptive skin toxicity treatment for anti-EGFR drugs: evaluation of efficacy of skin moisturizers and lymecycline. A phase II study.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) target therapies like erlotinib for metastatic lung cancer and cetuximab or panitumumab for metastatic colorectal cancer (mCRC) cause skin reaction that seems to be related to treatment efficacy. Skin toxicity evaluation protocol with panitumumab study has shown that preemptive treatment reduces the incidence of ≥Grade 2 (G2) skin toxicity in mCRC treated with panitumumab. Aim of this study is to evaluate if preemptive skin toxicity treatment with different drugs has good efficacy in patients receiving anti-EGFR therapies, such as cetuximab, panitumumab, and erlotinib, for mCRC and metastatic lung cancer. METHODS: Treatment included skin moisturizers with sunscreen and lymecycline 300 mg/daily. Primary objective is to reduce the incidence of ≥G2 skin toxicity during the first 3 months of therapy. Toxicities are reported with confidence interval at 95%. Quality of life was assessed with Dermatology Life Quality Index every 2 weeks and evaluated with repeated measure ANOVA. RESULTS: Fifty-one patients with mCRC (60.8%) and metastatic lung cancer (39.2%) were enrolled. Anticancer drugs were erlotinib/cetuximab/panitumumab 20:30:1. At 3-month evaluation, 27.4% patients had =G2 skin toxicity. Skin toxicity was not related with age (p = 0.67), sex (p = 0.65), previous chemotherapy regimens (p = 0.41), and current anti-EGFR treatment (p = 0.22). No gastrointestinal or hematological toxicities related to lymecycline were observed. Only six patients required further drugs. Quality of life analysis did not show a significant difference from the beginning and the end of treatment. CONCLUSIONS: Data show efficacy of preemptive treatment with a well-tolerated profile. A reduction of severe skin toxicities is shown with an increase of grade 1 toxicities, not leading to anti-EGFR dose reduction and with better quality of life for patients.

Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo.

BACKGROUND: Prostate carcinomas are androgen-dependent neoplasms which progress toward a hormone-independent phenotype during hormone-deprivation therapy. We evaluated nevirapine, a reverse transcriptase inhibitor, as a new treatment in hormone-refractory prostate carcinoma cells with the aim of restoring the androgen-dependency of tumor cells, the rationale being that endogenous reverse transcriptase is up-regulated in transformed cells and reverse transcriptase inhibitors exert a differentiating activity in human tumors. METHODS AND RESULTS: Nevirapine induced extensive reprogramming of gene expression in vitro with up-regulation of genes that might be silenced during prostate tumor progression (i.e., K18, PSA and androgen receptor) and down-regulation of genes involved in the progression toward an androgen-independent phenotype (i.e., K5, EGFR1, EGF and VEGF-A). Furthermore, nevirapine down-regulated the growth of prostate carcinoma xenografts in athymic mice and induced a differentiated phenotype in vivo with increased K18 expression. Interestingly, the drug restored androgen signaling by enhancing the ability of tumor cells to respond to dihydrotestosterone stimulation and to the antiproliferative activity of the androgen receptor blocker bicalutamide. Finally, nevirapine pretreatment increased the susceptibility of tumor cells to docetaxel, by enhancing their ability to undergo apoptosis. CONCLUSIONS: These data suggest that nevirapine may be clinically tested in human hormone-refractory prostate carcinoma to restore the susceptibility to androgen deprivation therapy or to docetaxel.